This is an open-label, Phase 1, first-in-human, dose-escalation study designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of the anti-Carcinoembryonic-antigen-related-cell-adhesion-molecule-6 (CEACAM6) antibody DNP002 in patients with advanced solid tumors.
The primary objectives of this study are to evaluate the safety and tolerability of DNP002 in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The secondary objectives are to evaluate the pharmacokinetic properties and preliminary anti-tumor effects in patients with solid tumors. The exploratory objectives are to analyze the expression and relationship with efficacy of various tumor and blood biomarkers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Anti-CEACAM6 monoclonal antibody
National Cancer Center
Goyang-si, Gyeonggi-do, South Korea
RECRUITINGDose-limiting toxicity
DLT is assessed according to NCI-CTCAE v5.0. The assessment is conducted only in the 2-week interval for subjects receiving the first dose (2-week interval subject) or the 3-week interval for subjects receiving the first dose (3-week interval subject).
Time frame: Up to 2 or 3 weeks
Incidence and severity of treatment emergent adverse events
Describe the character and incidence of toxicity based on CTCAE v5.0 that occur receiving DNP002.
Time frame: Up to 2 years
Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of DNP002
Samples for pharmacokinetic evaluation will be collected immediately prior to each of the 5 doses, and at predetermined time intervals after the 1st and 5th doses.
Time frame: Day 1 (pre-dose), 1 hour (post-dose), 2, 4, 8 10, 12 hours, Day 2, Day 3, Day 8 after 1st or 5th doses of the investigational drug.
Characterize peak plasma concentration (Cmax) of the pharmacokinetics (PK) of DNP002
Samples for pharmacokinetic evaluation will be collected immediately prior to each of the 5 doses, and at predetermined time intervals after the 1st and 5th doses.
Time frame: Day 1 (pre-dose), 1 hour (post-dose), 2, 4, 8 10, 12 hours, Day 2, Day 3, Day 8 after 1st or 5th doses of the investigational drug.
Overall response rate (ORR)
Percentage of patients whose best response to DNP002 is either a Complete response or Partial response, both defined according to RECIST or iRECIST criteria respectively.
Time frame: Up to 2 years
Leukocyte immune phenotyping
Whole blood flow cytometry analysis for characterization of blood leukocyte/lymphocyte including MDSC with regards to subpopulation and activation before and under treatment in all patients.
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Time frame: Day 1 (pre-dose), before the first, third, and fifth doses of the investigational drug, as well as 24 hours after the first and fifth doses.
Serum biomarkers
Total concentration of Arginase-1, soluble CEACAM6, CEA, Interferon-gamma and Interleukin-6 in serum derived from whole blood taken before and under treatment in all patients.
Time frame: Day 1 (pre-dose), before the first, third, and fifth doses of the investigational drug, as well as 4 hours after the first and fifth doses.
Concentration of anti-drug antibodies
Concentration in plasma
Time frame: Prior to administration at each dose (The investigational drug should be continued with dosing every two weeks as long as there is no disease progression or unacceptable toxicity.)